Autosampler seal pack for reducing a carryover percentage

ABSTRACT

A seal pack of a sample manager of a liquid chromatography system having a plurality of wash flow pathways fluidically connected to a central pathway that accommodates a sample needle, wherein a first wash flow pathway is vertically offset from a second wash flow pathway, such that a wash solution flows axially along an exterior surface of the sample needle in a vertical direction to wash the sample needle when flowing from the first wash flow pathway to the vertically offset second wash flow pathway, is provided. Furthermore, an autosampler and associated methods are also provided.

RELATED APPLICATIONS

This application is a non-provisional patent application claimingpriority to U.S. Provisional Patent Application No. 62/650,140, filedMar. 29, 2018, entitled “Autosampler Seal Pack For Reducing A CarryoverPercentage,” which is incorporated herein by reference.

FIELD OF TECHNOLOGY

The following relates to embodiments of a seal pack, and morespecifically to embodiments of a seal pack of an autosampler for liquidchromatography systems having an improved carryover percentage.

BACKGROUND

Liquid chromatography is a technique in analytic chemistry wheredistinct components of a mixture are identified by separating theindividual components by passing the mixture through an adsorbent mediumusing fluid flow so that the components elute at different rates. Liquidchromatography systems are typically comprised of a solvent deliverypump, an autosampler, a column, and a detector. The solvent deliverypump pumps mobile phase fluid through the system, the autosamplerintroduces the sample to be analyzed to the analytic flow path, thecolumn contains the adsorbent packing material used to effectseparation, and the detector detects the separated components as theyelute out of the column.

In certain liquid chromatography systems, seal packs are a part of theautosampler that is responsible for making a high-pressure seal with theouter diameter of the sample needle to allow for injection of a sampleinto an analytic flow stream. Further, the seal pack is responsible forwashing the sample needle with a solvent from a wash reservoir. Thesample needle is washed to remove/clean remaining sample from a previousrun. Sample leftover on the sample needle may increase a carryoverpercentage, which is the presence of an analyte after a blank having nosample is injected into the analytic flow path. A carryover percentageabove certain limits can adversely affect the analytical data obtainedfrom the liquid chromatography run.

Thus, a need exists for improving a washing of the sample needle toreduce a carryover percentage.

SUMMARY

A first aspect relates generally to a seal pack of a sample manager of aliquid chromatography system, the seal pack comprising: a plurality ofwash flow pathways fluidically connected to a central pathway thataccommodates a sample needle, wherein a first wash flow pathway isvertically offset from a second wash flow pathway, such that a washsolution flows axially along an exterior surface of the sample needle ina vertical direction to wash the sample needle when flowing from thefirst wash flow pathway to the vertically offset second wash flowpathway.

In addition or alternatively, the wash solution flows within the centralpathway between the first wash flow pathway and the second wash flowpathway.

In addition or alternatively, the wash solution washes the sample needleas the sample needle moves vertically within the seal pack.

In addition or alternatively, the seal pack includes an upper bodyportion, a middle portion, and a lower body portion, which form ageneral body structure of the seal pack.

In addition or alternatively, the first wash flow pathway and the secondwash flow pathway are both disposed within the upper body portion.

In addition or alternatively, the first wash flow pathway includes awash inlet fluidically connected to an external wash reservoir of theliquid chromatography system.

In addition or alternatively, the exterior surface of the sample needleis simultaneously cleaned by the wash solution at two differentsubsections of the exterior surface of the surface needle.

In addition or alternatively, the two different subsections of theexterior surface of the sample needle being simultaneously cleaned arelocated above and below a high-pressure seal arrangement within the sealpack, respectively.

In addition or alternatively, a carryover percentage is equal to or lessthan 0.0025%.

A second aspect relates generally to a seal pack of a sample manager ofa liquid chromatography system, the seal pack having an upper bodyportion, a middle body portion, and a lower body portion, which forms ageneral body structure of the seal pack, the seal pack comprising: acentral flow path extending vertically through the seal pack, thecentral flow path accommodating a sample needle, a wash inlet disposedin the upper body portion, configured to receive a wash solution, thewash inlet connecting to the central flow path, a first wash pathdisposed in the upper body portion and connected to the central flowpath, the first wash path being vertically offset from the wash inlet, aconnecting wash path extending through the upper body portion, themiddle body portion, and the lower body portion, the connecting washpath connecting the first wash path to a second wash path disposed inthe lower body portion, wherein the second wash path is connected to thecentral flow path, a third wash path disposed in the lower body portion,the third wash path being vertically offset from the second wash path,and a wash outlet disposed in the middle body portion, the wash outletbeing fluidically connected to a suction pump for drawing the washsolution through the seal pack.

In addition or alternatively, when the wash solution flows from the washinlet to the first wash path, the wash solution flows axially along thesample needle in a vertical direction to directly wash the sampleneedle.

In addition or alternatively, when the wash solution flows from thesecond wash path to the third wash path, the wash solution flows axiallyalong the sample needle in a vertical direction to directly wash thesample needle.

In addition or alternatively, the seal pack does not include a lowerwash frit.

In addition or alternatively, the seal pack includes an upper wash fritretainer and an upper wash frit, wherein the sample needle passesthrough the upper wash frit.

In addition or alternatively, the seal pack includes a bushing disposedwithin the lower body portion, the bushing having a central bore forreceiving the sample needle as the sample needle moves toward a samplesource.

In addition or alternatively, the bushing is comprised of a non-metalmaterial and prevents damage to the sample needle from contacting ametal surface of the seal pack as the sample needle moves towards andaway from the sample source.

In addition or alternatively, the wash solution is flowing through theseal pack as the sample needle is moving within the seal pack.

In addition or alternatively, the seal pack includes a firsthigh-pressure seal and a second high-pressure seal, the firsthigh-pressure seal and the second high-pressure seal are disposed withinthe middle body portion, and form a seal around the sample needle at apoint where a sample is injected into an analytic flow path.

In addition or alternatively, a carryover percentage is equal to or lessthan 0.0025%.

A third aspect relates generally to an autosampler of a liquidchromatography system, comprising: a sample needle, the sample needleconfigured to aspirate a sample from at least one sample source andinject the sample into an analytic flow path of the liquidchromatography system, a seal pack, the seal pack comprising a pluralityof wash flow pathways fluidically connected to a central pathway thataccommodates the sample needle, wherein a first wash flow pathway isvertically offset from a second wash flow pathway, a pump delivering amobile phase to the seal pack, and a needle wash pump fluidicallyconnected to the seal pack to draw a wash solution through the pluralityof wash flow pathways of the seal pack and into a waste reservoir,wherein, when the needle wash pump draws the wash solution through theplurality of wash flow pathways, a wash solution flows axially along anexterior surface of the sample needle in a vertical direction to washthe sample needle when flowing from the first wash flow pathway to thevertically offset second wash flow pathway.

In addition or alternatively, the wash solution flows within the centralpathway between the first wash flow pathway and the second wash flowpathway.

In addition or alternatively, the first wash flow pathway and the secondwash flow pathway are both disposed within an upper body portion of theseal pack.

In addition or alternatively, the first wash flow pathway includes awash inlet fluidically connected to the wash reservoir.

In addition or alternatively, the exterior surface of the sample needleis simultaneously cleaned by the wash solution at two differentsubsections of the exterior surface of the surface needle.

In addition or alternatively, the two different subsections of theexterior surface of the sample needle being simultaneously cleaned arelocated above and below a high-seal arrangement within the seal pack,respectively.

A fourth aspect relates generally to a method of washing a sample needleof a liquid chromatography system, the method comprising: directing awash fluid axially along an exterior surface of a sample needlecontained within a central pathway of a seal pack, the central pathwayguiding the sample needle in a vertical only direction, wherein thedirecting the wash solution axially along the exterior surface of theneedle includes: connecting a wash fluid inlet flow path located in anupper body portion of the seal back to the central pathway, andvertically offsetting a wash flow path located within the upper bodyportion from the wash fluid inlet flow path along the central pathway,wherein a needle wash pump fluidically connected to a wash flow outletdisposed within the seal pack is configured to draw the wash solutionfrom the wash fluid inlet flow path through the central pathway againstthe exterior surface of the sample needle to the wash flow path.

In addition or alternatively, the directing the wash solution axiallyalong the exterior surface of the needle further includes:interconnecting the wash flow path located in the upper body portion ofthe seal pack with a first wash flow path located in a lower bodyportion of the seal pack; connecting the first wash flow path to thecentral pathway; and vertically offsetting a second wash flow pathlocated in the lower body portion of the seal pack from the first washflow path along the central pathway.

In addition or alternatively, the wash fluid washes the sample needle asthe sample needle moves vertically within the central pathway.

In addition or alternatively, the wash fluid outlet is located in amiddle portion of the seal pack.

In addition or alternatively, the method further includes drawing airthrough a bushing disposed in the lower body portion of the seal pack asthe wash fluid is drawn through the seal pack to reduce an overallsolvent consumption rate as a needle wash pump is turned on.

In addition or alternatively, the method further includes disposing abushing having a bore for receiving the sample needle in the lower bodyportion of the seal pack, the bushing preventing the sample needle fromcontacting a surface of the lower body portion of the seal pack as thesample needle moves vertically in and out of the seal pack to aspirate asample.

In addition or alternatively, a carryover percentage is equal to or lessthan 0.0025%.

A fifth aspect relates to a wash sequence for washing a sample needle ofan autosampler of a liquid chromatography system, the wash sequencecomprising: continuously washing an exterior surface of the sampleneedle contained within a seal pack of the autosampler as the sampleneedle moves toward a sample source located proximate the seal pack, fora predetermined amount of time.

In addition or alternatively, the exterior surface of the sample needleis washed as the sample needle moves up and away from the sample source.

In addition or alternatively, in a first sequence, the predeterminedamount of time is between 3-4 seconds, as the sample needle moves frominside the seal pack to the sample source.

In addition or alternatively, in a second sequence, the predeterminedamount of time is between 14-16 seconds, as the sample needle movestowards the sample source.

In addition or alternatively, in the second sequence, a movement speedof the sample needle from inside the seal pack to the sample source isreduced to extend the predetermined amount of time, as compared to amovement speed of the sample needle in the first sequence.

In addition or alternatively, in a third sequence, the predeterminedamount of time is equivalent to the second sequence, and also includesan additional washing step for a predetermined amount of time as thesample needle moves away from the sample source.

In addition or alternatively, the predetermined amount of time of theadditional washing step is equivalent to the predetermined amount oftime for the second sequence.

In addition or alternatively, the continuous washing of the exteriorsurface of the sample needle occurs axially along the sample needle in avertical direction, within a central pathway of the seal pack.

In addition or alternatively, a wash fluid directly contacts theexterior surface of the sample needle during the continuous washing.

In addition or alternatively, the sample needle only moves up and downwithin the seal pack during the continuous washing.

In addition or alternatively, the sample needle is not relocated to aseparate component for washing, and remains within a central pathway ofthe seal pack.

In addition or alternatively, a carryover percentage is equal to or lessthan 0.0025%.

The foregoing and other features of construction and operation will bemore readily understood and fully appreciated from the followingdetailed disclosure, taken in conjunction with accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Some of the embodiments will be described in detail, with reference tothe following figures, wherein like designations denote like members,wherein:

FIG. 1 depicts a fluidics diagram of an autosampler of a liquidchromatography system having a seal pack, in accordance with embodimentsof the present invention;

FIG. 2 depicts a cross-section view of a conventional seal pack;

FIG. 3 depicts a wash cycle for the current seal pack of FIG. 2, when asample needle is in a first position;

FIG. 4 depicts a wash cycle for the current seal pack of FIG. 2, whenthe sample needle is in a second position;

FIG. 5 depicts a cross-sectional-view of a seal pack 100, in accordancewith embodiments of the present invention;

FIG. 6 depicts a wash cycle through the seal pack of FIG. 5, when thesample needle is in a first position, in accordance with embodiments ofthe present invention;

FIG. 7 depicts a wash cycle through the seal pack of FIG. 5, when thesample needle is in a second position, in accordance with embodiments ofthe present invention;

FIG. 8 depicts a wash cycle through the seal pack of FIG. 5, when thesample needle has returned to the first position, in accordance withembodiments of the present invention; and

FIG. 9 depicts a graphical illustration of achieving a carryoverpercentage below 0.0025% using the seal pack of FIG. 5, in accordancewith the embodiments of the present invention.

The cross-sectional views are composite images, as internal features maybe in three different sectional planes.

DETAILED DESCRIPTION

A detailed description of the hereinafter described embodiments of thedisclosed apparatus and method are presented herein by way ofexemplification and not limitation with reference to the Figures.Although certain embodiments are shown and described in detail, itshould be understood that various changes and modifications may be madewithout departing from the scope of the appended claims. The scope ofthe present disclosure will in no way be limited to the number ofconstituting components, the materials thereof, the shapes thereof, therelative arrangement thereof, etc., and are disclosed simply as anexample of embodiments of the present disclosure.

As a preface to the detailed description, it should be noted that, asused in this specification and the appended claims, the singular forms“a”, “an” and “the” include plural referents, unless the context clearlydictates otherwise.

Referring to the drawings, FIG. 1 depicts a fluidics diagram of anautosampler of a liquid chromatography system 10 having a seal pack 100,in accordance with embodiments of the present invention. An entireliquid chromatography system may not be shown in FIG. 1, but system 10may also include conventional components of a liquid chromatographysystem not shown, such as a column, detector, solvent reservoir, etc.Embodiments of the liquid chromatography system 10 may include a valveV1 (e.g. high-pressure needle valve) fluidically connected to a pump,such as a solvent delivery pump, a valve V2 (high-pressure needlevalve), a valve V3 (e.g. two-way solenoid valve) fluidically connectedto the valve V2, a valve V4 (e.g. three-way solenoid valve), a pressuretransducer, a sample loop, a flow restrictor, a seal pack 100, a sampleneedle 160, a sample source (e.g. sample vial), a wash reservoir, aneedle wash pump, one or more waste reservoirs, and a sample syringe Inthe system 10, a movement of the sample needle 160 may be limited tovertical movement. For example, the sample needle 160 may not move inany other direction but up and down, to aspirate a sample from a samplesource and inject the sample into an analytic flow path, within the sealpack 100. Embodiments of system 10 may further include a carousel ofsample vials that may rotate underneath the seal pack 100 to bring theproper sample source (e.g. sample vial) into alignment with the sampleneedle 160 of the seal pack 100. Once aligned, the sample needle 160 maybe dropped down through the seal pack 100 into the sample source toaspirate the sample into the sample needle 100 and into the sample loop.The sample is aspirated through a side port opening disposed a distancefrom the tip of the sample needle 160, and when the sample needle 160enters the sample source, some sample contacts and may remain on theexterior surface of the sample needle 160, which may contaminate resultsor otherwise adversely affect a carryover percentage. After aspiratingthe sample, the sample needle 160 may then be pulled back up furtherinto the seal pack 100 to inject the sample into a high-pressureanalytic flow path.

The seal pack 100 shown in FIG. 1 may include high-pressure seals (shownschematically as two rectangles in the seal pack). The high-pressureseals are arranged against an outer diameter of the sample needle 160 toallow the sample to be injected through a side port of the sample needle160 into the high-pressure flow path. The high-pressure flow path comesinto the seal pack 100 on side/point of the seal pack 100 (e.g. frompump and through flow restrictor) and exits another side/point of sealpack 100 to the column. The high-pressure flow path is fluidicallyconnected to the seal pack 100 through a small chamber surrounded by thetwo high-pressure seals. After aspirating the sample from the samplesource, the sample needle 160 may be brought back up so that the sideport is positioned within the chamber surrounded by the high-pressureseals to inject the sample into the high-pressure analytic flow path.

Furthermore, when valve V1 is closed, the high-pressure flow may beallowed to flow from the pump to the flow restrictor and into the sealpack 100. When valve V1 is open, the flow of the solvent/mobile phasemay split such that a portion of the mobile phase is passing through tothe flow restrictor and a portion is flowing towards valve V2. Whenvalve V2 is open, flow may continue towards the pressure transducer andto the sample loop, and may connect the sample syringe. To start theinjection, the sample needle 160 is in the seal pack, V2 is closed, andV1 is opened. The flow coming from the pump now splits as valve V1 isopen, and small percentage of the flow will go through the flowrestrictor and the rest of the flow will flow through valve V2 and tothe pressure transducer and to the sample loop and into the needle 160,and leave the sample needle 160 through the side port of the sampleneedle 160 positioned between the two high-pressure seals, and then intothe column. The flow of the mobile phase through the sample loop maypush the sample in the sample loop and the sample needle out through theside port opening of the sample needle 160 and into the analytic flowpath.

The seal pack 100 depicted schematically in FIG. 1 may house, contain,or otherwise accommodate the sample needle 160 during the injectionprocess. Embodiments of the seal pack 100 may also have a wash fluidpathway configuration that improves upon current sample needle washingto reduce a carryover percentage of the system 10. Current sample needlewashing fails to directly wash an exterior surface of the sample needle,among other things.

FIG. 2 depicts a cross-section view of current seal pack 1. Seal pack 1includes an upper body portion 10, a middle body portion 20, and a lowerbody portion 30. The seal pack 1 may house, seal, accommodate, receive,etc. a sample needle 60. The seal pack 1 may also include an upper frit15 and a lower frit 35. FIG. 3 depicts a wash cycle for the current sealpack 1 of FIG. 2, when the sample needle 60 is in a first position.During a wash cycle, a wash fluid 5 enters the seal pack 1 via washinlet 41 and flow through the wash inlet pathway and then through aconnection pathway 42 to a wash outlet pathway and exits the seal pack 1via wash outlet 43. As the wash fluid 5 flows through the wash outletpathway, the wash fluid 5 only cleans the lower frit 35, and does notdirectly clean an exterior surface of the sample needle 60 as the sampleneedle 60 is held in the first position above the lower frit 35 for apredetermined amount of time. Thus, for a predetermined amount of timethat the wash fluid 5 is flowing through the seal pack 1, only the lowerwash frit 35 is being contacted with wash fluid 5. However, even whenthe sample needle 60 is lowered to a second position passing through thelower frit 35 to aspirate a sample, the sample needle 60 is not directlycontacted with the wash fluid 5. FIG. 4 depicts a wash cycle for thecurrent seal pack 1 of FIG. 2, when the sample needle 60 is in a secondposition. As shown in FIG. 4, with the current design of seal pack 1,the wash fluid 5 flows around the lower frit 35 and into cavity 45 toexit the seal pack 1 via the wash outlet 43, avoiding direct contactwith a surface of the sample needle 60. For instance, nothing is forcingthe wash fluid 5 to flow through the lower wash frit 35, but rather thewash fluid 5 flows around the circular lower wash frit 35 through theannular cavity or gap 45 formed between the lower wash frit 35 and/or alower wash frit retainer surrounding or partially surrounding the lowerwash frit 35 and the lower body portion 20. As a result, the sampleneedle 60 may not be washed/cleaned well enough to remove sample residueleft over from sample aspiration, thereby increasing a probability ofcarryover.

Referring still to the drawings, FIG. 5 depicts a cross-sectional-viewof a seal pack 100, in accordance with embodiments of the presentinvention. Embodiments of the seal pack 100 may be a component in theliquid chromatography system depicted in FIG. 1. Embodiments of the sealpack 100 may include an upper frit retainer 116, an upper frit 115, anupper body portion 110, a middle body portion 120, a high-pressure sealarrangement 125 (e.g. an upper high-pressure seal and a lowerhigh-pressure seal), a lower body portion 130, and a bushing 135disposed within the lower body portion 130. Embodiments of the upperbody portion 110, the middle body portion 120, and the lower bodyportion 130 may be operably coupled to each other to form a general bodystructure of the seal pack 100. For example, the upper body portion 110,the middle body portion 120, and the lower body portion 130 may befastened together, coupled together, attached together, adheredtogether, or in some embodiments, may be structurally integral.Embodiments of the upper body portion 110, the middle body portion 120,and the lower body portion 130 may be comprised of a metal, such asstainless steel.

Embodiments of the seal pack 100 may not include a lower wash frit, suchas lower wash frit 35 of seal pack 1 shown in FIGS. 2-4. Embodiments ofthe seal pack 100 may include a bushing 135 pressed-in to a cavity ofthe lower body portion 130. The bushing 135 may be a generally annularcomponent made on a non-metal material, such as Teflon®. The bushing 135may be disposed within the lower body portion, and have a central borefor receiving the sample needle 160 as the sample needle 160 movestoward a sample source. Because the bushing 135 may be comprised of anon-metal material, the bushing 145 may prevent damage to the sampleneedle 160 from contacting a metal surface of the seal pack 100 (i.e.lower body portion 130) as the sample needle 160 moves towards and awayfrom the sample source. Additionally, air may be drawn through thebushing 135 disposed in the lower body portion 130 of the seal pack 100as wash fluid 5 is drawn through the seal pack 100 to reduce an overallsolvent consumption rate as a needle wash pump is turned on. Further,the seal arrangement 135 of the seal pack 100 may include a firsthigh-pressure seal and a second high-pressure seal disposed within orproximate the middle body portion 120, forming a seal around the sampleneedle 160 at a point where a sample is injected into an analytic flowpath, as described above with respect to FIG. 1.

Moreover, embodiments of the seal pack 100 may include a plurality ofwash flow pathways fluidically connected to a central pathway 165 thataccommodates a sample needle 160, wherein a first wash flow pathway isvertically offset from a second wash flow pathway, such that a washsolution flows axially along an exterior surface of the sample needle160 in a vertical direction to wash the sample needle 160 when flowingfrom the first wash flow pathway to the vertically offset second washflow pathway. In an exemplary embodiment, the seal pack 100 may have anupper body portion 110, a middle body portion 120, and a lower bodyportion 130, which forms a general body structure of the seal pack 100,the seal pack 100 including a central flow path 165 extending verticallythrough the seal pack 100, the central flow path 165 accommodating thesample needle 160, a wash inlet 141 disposed in the upper body portion110, configured to receive a wash solution 5, the wash inlet 141connecting to the central flow path 165 via flow path 142, a first washpath 143 disposed in the upper body portion 120 and connected to thecentral flow path 165, the first wash path 143 being vertically offsetfrom the wash inlet 141, a connecting wash path 144 extending throughthe upper body portion 110, the middle body portion 120, and the lowerbody portion 130, the connecting wash path 144 connecting the first washpath 143 to a second wash path 145 disposed in the lower body portion130, wherein the second wash path 145 is connected to the central flowpath 165, a third wash path 146 disposed in the lower body portion 130,the third wash path 146 being vertically offset from the second washpath 145, and a wash outlet 149 disposed in the middle body portion 120,the wash outlet 149 being fluidically connected to a suction pump fordrawing the wash solution 5 through the seal pack 100. Embodiments ofthe flow paths 141, 142, 143, 144, 145, 146, 147, 148, 149 may be paths,fluid pathways, pathways, bores, channels, tubes, connection lines,tunnels, and the like.

Embodiments of the seal pack 100 may include a central pathway 165.Embodiments of the central pathway 165 may be a channel, a tube, a path,a pathway, a fluid path, a fluid pathway, bore, tunnel, and the like,which may extend vertically along vertical axis 3. The central pathway165 may be positioned at a center location of the seal pack 100.Further, embodiments of the central pathway 165 may receive,accommodate, contain, guide, hold, etc. the sample needle 160, as shownin FIGS. 6-7. For instance, the sample needle 160 may move up and downwithin the central pathway 165 along the vertical axis 3. In anexemplary embodiment, the sample needle 160 may only move verticallyalong vertical axis 3 to aspirate and inject the sample, and during washcycles. The sample needle 160 may be washed without having to move thesample needle 160 to another physical location outside of the seal pack100. Embodiments of the seal pack 100 may include a wash inlet 141.Additionally, the central pathway 165 may extend through the upper bodyportion 110, the middle body portion 120, the lower body portion 130,and the bushing 135. An end of the central pathway 165 proximate orotherwise near an end face of the busing 135 may include an opening thatallows the sample needle 160 to exit the seal pack 100 for sampleaspiration.

Embodiments of the seal pack 100 may include a wash inlet 141.Embodiments of the wash inlet 141 may be an inlet or opening proximateor at an external surface of the seal pack 100, which may be in fluidcommunication with a wash fluid or wash reservoir or wash source. Thewash inlet 141 may be disposed within the upper body portion 110,configured to allow a wash solution or wash fluid to enter the interiorof the seal pack 100. In alternative embodiments, the wash inlet 141 maybe disposed in the lower body portion 130 or the middle body portion120. The wash inlet 141 may also include a wash inlet flow path 142 thatmay extend within the seal pack 100 to fluidically and physicallyconnect the wash inlet 141 to the central pathway 165. Furthermore,embodiments of the seal pack 100 may include a wash flow path 143 (e.g.a first wash flow path). Embodiments of the wash flow path 143 may bedisposed within the same body portion of the seal pack 100 (e.g. upperbody portion 110) as the wash inlet 141 and wash inlet flow path 142.The wash flow path 143 may be fluidically and physically connected tothe central pathway 165, extending from the central pathway 165. Forinstance, the wash flow path 143 may extend horizontally from thecentral pathway 165. The wash flow path 143 may be in fluidcommunication or fluidically connected to the wash inlet flow path 142,via the central pathway 165. In an exemplary embodiment, the wash flowpath 143 may be vertically offset from the wash inlet flow path 142and/or wash inlet 141. For example, the flow path 143 may beinterconnected with the central pathway 165 at a different point alongthe central pathway 165 than the wash inlet flow path 142 and/or washinlet 141, such that a vertical distance of the central pathway 165separates the flow path 143 and the wash inlet flow path 142/wash inlet141. The offsetting of the flow paths creates a section of the centralpathway 165 that wash fluid may travel through to get from the washinlet flow path 142 to the wash flow path 143. As the wash fluid travelsthrough the central pathway 165 between the flow paths 143, 142, thewash fluid washes the sample needle axially across the exterior surfaceof the sample needle 160, above the high-pressure seal arrangement 125.

Referring still to FIG. 1, embodiments of the seal pack 100 may includea connecting wash path 144. Embodiments of the connecting wash path 144may interconnect physically and fluidically the wash flow path 143 andthe wash flow path 145 (e.g. a second wash flow path). Embodiments ofthe connecting wash path 144 may be a connection path, a connector, awash tube, a connection tube, an interconnection, and the like,configured to provide a fluid flow path between the wash flow path 143and wash flow path 145. The connecting wash path 144 may extend in avertical direction, parallel to vertical axis 3 through the upper bodyportion 110, the middle body portion 120, and the lower body portion130. In an exemplary embodiment, the connecting wash path 144 may be astraight pathway extending parallel to the vertical axis 3. In otherembodiments, the connecting path 144 may be curved or otherwise includea stepped configuration between the wash flow path 143 and the wash flowpath 145. Further, a seal or washer may be disposed between the upperbody portion 110 and the middle body portion 120 at a point where theconnecting wash path 144 extends therethrough, and likewise between themiddle body portion 120 and the lower body portion 130 where theconnecting wash path 144 extends therethrough. Moreover, the wash flowpath 145 may be fluidically and physically connected to the centralpathway 165. The wash flow path 145 may be disposed in the lower bodyportion 130 of the seal pack 100.

Embodiments of the seal pack 100 may further include a wash flow path146 (e.g. a third wash flow path). Embodiments of the wash flow path 146may be disposed within the same body portion of the seal pack 100 (e.g.lower body portion 130) as the wash flow path 145. The wash flow path146 may be fluidically and physically connected to the central pathway165, extending from the central pathway 165. For instance, the wash flowpath 146 may extend horizontally from the central pathway 165. The washflow path 146 may be in fluid communication or fluidically connected tothe wash flow path 145, via the central pathway 165. In an exemplaryembodiment, the wash flow path 146 may be vertically offset from thewash inlet path 145. For example, the flow path 146 may beinterconnected with the central pathway 165 at a different point alongthe central pathway 165 than the wash flow path 145, such that avertical distance of the central pathway 165 separates the flow path 146and the wash flow path 145. The offsetting of the flow paths creates asection of the central pathway 165, which may be discrete and distinctfrom the section of the central pathway 165 between path 142 and 143,that wash fluid may travel through to get from the wash flow path 145 tothe wash flow path 146. As the wash fluid travels through the centralpathway 165 between the flow paths 145, 146, the wash fluid washes thesample needle axially across the exterior surface of the sample needle160, below the high-pressure seal arrangement 125.

Additionally, embodiments of the seal pack 100 may include wash outlet149. Embodiments of the wash outlet 149 may be an outlet or openingproximate or at an external surface of the seal pack 100, which may bein fluid communication with a needle wash pump and a waste washreservoir. For instance, a needle wash pump, which may be one or morepumps, may be connected to the wash outlet 149, and create a suctionforce sufficient to create a vacuum within the seal pack 100 and to drawthe wash fluid from the needle wash reservoir and into the wash inlet141, as schematically depicted in FIG. 1. The wash outlet 149 may bedisposed within the middle body portion 120, configured to allow a washsolution or wash fluid to exit the interior of the seal pack 100. Inalternative embodiments, the wash outlet 149 may be disposed in thelower body portion 130 or the upper body portion 110. The wash outlet149 may also include a wash outlet flow path 148 that may extend withinthe seal pack 100 to fluidically and physically connect the wash outlet149 to an intermediate wash flow path 147. The intermediate wash flowpath 147 may connect the wash flow path 146 to the wash outlet flow path147 and ultimately the wash outlet 149. The intermediate flow path 147may extend across multiple body portions of the seal pack 100, such asthe lower body portion 130 and the middle body portion 120. At thesepoints where the intermediate flow path 147 extends across the bodyportions of the seal pack 100, a washer or seal may be disposed.

Accordingly, embodiments of the seal pack 100 may include a wash fluidflow path configuration that promotes direct contact between the washfluid 5 and the sample needle 160, such that the wash fluid 5 flowsaxially along a length of the exterior surface of the sample needle 160simultaneously or otherwise at one or more locations (e.g. above andbelow high-pressure seal arrangement 125). FIG. 6 depicts a wash cyclethrough the seal pack 100 when the sample needle 160 is in a firstposition, in accordance with embodiments of the present invention. Inthe first position, a tip of the sample needle 160 is positioned abovethe bushing 135 of the lower body portion 130, within the centralpathway 165 of the lower body portion 130. If a wash cycle is initiatedwhile the sample needle 160 is in the first position shown in FIG. 6,the sample needle 160 may still be washed by the wash fluid 5, axiallyalong the exterior surface of the sample needle 160. A wash fluid 5 maybe drawn in to the wash inlet 141 by suction forces created when theneedle wash pump is activated and the valve V4 associated with theneedle wash reservoir is in a position to allow flow of the wash fluid 5from the wash reservoir. The wash fluid 5 may flow through the washinlet 141 and through the wash inlet flow path 142 to the centralpathway 165 where the wash inlet flow path 142 intersections or connectswith the central pathway 165. The wash fluid 5 may thus flow axiallyalong and against a length of the exterior surface of the sample needle160 through the central pathway 165 in a vertical direction (e.g. up)along axis 3 to the wash flow path 143. The flow of the wash fluid 5axially across the sample needle 160 may act to clean and/or wash thesample needle 160 to help remove unwanted sample from previous runs thatmay have contacted the sample needle 160. The wash fluid 5 may continueflowing through the wash flow path 143 and through the connecting washpath 144 to reach the wash flow path 145. Because there is no lower washfrit, the wash fluid 5 continues through wash flow path 145 and may flowaxially along and against a length of the exterior surface of the sampleneedle 160 through the central pathway 165 in a vertical direction (e.g.down) along axis 3 to the wash flow path 146. The flow of the wash fluid5 axially across the sample needle 160 may act to clean and/or wash thesample needle 160 to help remove unwanted sample from previous runs thatmay have contacted the sample needle 160. The wash fluid may then flowthrough the wash flow path 146 and exit via the wash outlet 149. In anexemplary embodiment, the wash fluid 5 may flow through the intermediatewash flow path 147 to the wash outlet flow path 148 and out through theoutlet 149 to a wash waste reservoir. Thus, when the sample needle 160is in the first position, prior to aspirating a sample from a samplesource, the wash fluid 5 may be directly contacting the surface of thesample needle 160 to provide washing/cleaning benefits.

FIG. 7 depicts a wash cycle through the seal pack of FIG. 5, when thesample needle is in a second position, in accordance with embodiments ofthe present invention. The flow path of the wash fluid 5 may be the sameor substantially the same as when the sample needle 160 is in the firstposition. However, the wash fluid 5 may be flowing through the seal pack100 as the sample needle moves from the first position shown in FIG. 6to the second position shown in FIG. 7. To achieve the second position,the sample needle 160 is lowered or otherwise moved in a direction D(e.g. vertically along axis 3) towards a sample source, and eventuallyinto a sample source (e.g. sample vial) to aspirate the sample. Thus, inexemplary embodiments, the sample needle 160 is being directly contactedwith the wash fluid 5 axially along a length of the exterior surface ofthe sample needle 160 to remove sample from the exterior surface of thesample needle 160 and ultimately reduce a carryover percentage. Becausethe sample needle 160 is moving in direction D from the first positionto the second position, and the wash fluid 5 flows axially along thesample needle 160 through sections of the central pathway 165, a surfacearea of the exterior surface of the sample needle 160 being cleaned isincreased and overall exposure of the sample needle 160 to the washfluid 5 is increased throughout the wash cycle.

FIG. 8 depicts a wash cycle through the seal pack of FIG. 5, when thesample needle has returned to the first position, in accordance withembodiments of the present invention. The flow path of the wash fluid 5may be the same or substantially the same as when the sample needle 160is in the first position and second position. However, the wash fluid 5may be flowing through the seal pack 100 as the sample needle 160 movesfrom the second position shown in FIG. 7 back to the second positionshown in FIG. 8. To return to the first position from the secondposition, the sample needle 160 is raised or otherwise moved in adirection D (e.g. vertically along axis 3) away from a sample source toeventually inject the sample into the high-pressure analytic flow pathflowing through the seal pack 100 and ultimately to the column of theliquid chromatography system. Thus, in exemplary embodiments, the sampleneedle 160 is being directly contacted with the wash fluid 5 axiallyalong a length of the exterior surface of the sample needle 160 toremove sample from the exterior surface of the sample needle 160 andultimately reduce a carryover percentage. Because the sample needle 160is moving in direction D from the second position to the first position,and the wash fluid 5 flows axially along the sample needle 160 throughsections of the central pathway 165, a surface area of the exteriorsurface of the sample needle 160 being cleaned is increased and overallexposure of the sample needle 160 to the wash fluid 5 is increasedthroughout the wash cycle.

In alternative embodiments, the seal pack 100 may include one or moreflow paths in addition to the flow paths shown in FIGS. 5-8. Forexample, embodiments of the seal pack 100 may have a wash flow pathconfiguration that directs the wash fluid 5 to flow through the centralpathway 165 at more than two distinct and discrete locations. Further,embodiments of the seal pack 100 may include a wash flow pathconfiguration that only washes the sample needle 160 above thehigh-pressure seal arrangement 125 or only below the high-pressure sealarrangement 125.

Referring now to FIGS. 1 and 5-8, embodiments of the seal pack 100 maybe a part of an autosampler or sample manager of a liquid chromatographysystem 10. In an exemplary embodiment, an autosampler of a liquidchromatography system may include a sample needle 160 configured toaspirate a sample from at least one sample source and inject the sampleinto an analytic flow path of the liquid chromatography system, and aseal pack 100 comprising a plurality of wash flow pathways fluidicallyconnected to a central pathway that accommodates the sample needle,wherein a first wash flow pathway is vertically offset from a secondwash flow pathway. Embodiments of the autosampler may also include apump delivering a mobile phase to the seal pack 100, and a needle washpump fluidically connected to the seal pack 100 to draw a wash solution5 through the plurality of wash flow pathways of the seal pack 100 andinto a waste reservoir. In the autosampler of exemplary embodiments ofthe present invention, when the needle wash pump draws the wash solutionthrough the plurality of wash flow pathways, a wash solution flowsaxially along an exterior surface of the sample needle in a verticaldirection to wash the sample needle when flowing from the first washflow pathway to the vertically offset second wash flow pathway.

Furthermore, a method of washing a sample needle 160 of a liquidchromatography system may include a step of directing a wash fluid 5axially along an exterior surface of a sample needle 160 containedwithin a central pathway 165 of a seal pack 100, the central pathway 165guiding the sample needle 160 in a vertical only direction. Embodimentsof the step of directing the wash solution 5 axially along the exteriorsurface of the needle 160 may include multiple steps. For instance, thestep of directing the wash solution 5 axially along the sample needle160 may include a step of connecting a wash fluid inlet flow path 142located in an upper body portion 110 of the seal pack 100 to the centralpathway 165. The directing may also include a step of verticallyoffsetting a wash flow path 143 located within the upper body portion110 from the wash fluid inlet flow path 142 along the central pathway165, and/or vertically offsetting a wash flow path 146 located withinthe lower body portion 130 from a wash flow path 145 also located in thelower body portion, along the central pathway 165. The directing stepmay also include fluidically connecting a wash flow outlet disposedwithin the seal pack 100 to draw the wash solution 5 into the wash fluidinlet flow path 142/141 and through the central pathway against theexterior surface of the sample needle 160 to the wash flow paths of theseal pack 100. The step of directing may also include the steps ofinterconnecting the wash flow path 143 located in the upper body portion110 of the seal pack 100 with a first wash flow path 145 located in alower body portion 130 of the seal pack 100, connecting the first washflow path 145 to the central pathway 165, and vertically offsetting asecond wash flow path 146 located in the lower body portion 130 of theseal pack 100 from the first wash flow path 145 along the centralpathway 165. Moreover, embodiments of the method of washing the sampleneedle 100 may also include a step of disposing a bushing 135 having abore for receiving the sample needle 160 in the lower body portion 120of the seal pack 100, the bushing 135 preventing the sample needle 160from contacting a surface of the lower body portion 130 of the seal pack100 as the sample needle 160 moves vertically in and out of the sealpack 100 to aspirate a sample. The method may also include a step ofdrawing air through an opening in the bushing 135 disposed in the lowerbody portion 130 of the seal pack 100 as the wash fluid 5 is drawnthrough the seal pack 100 to reduce an overall solvent consumption rateas a needle wash pump is turned on. The method may achieve a carryoverpercentage equal to or less than 0.0025%.

Furthermore, seal pack 100 may be conducive to applying new washsequences that can reduce a carryover percentage. An exemplary washsequence for washing a sample needle of an autosampler of a liquidchromatography system may include continuously washing an exteriorsurface of the sample needle 160 contained within a seal pack 100 of theautosampler as the sample needle 160 moves toward a sample sourcelocated proximate the seal pack 100, for a predetermined amount of time.During the wash sequence, the exterior surface of the sample needle 160may be washed as the sample needle 160 moves up and away from the samplesource. The wash sequence may include more than one modes or sequences.For example, the wash sequence may include a “normal” sequence, a“double” sequence, and an “extended” sequence.

In the normal sequence, the predetermined amount of time of washing thesample needle 160 may be between 3-4 seconds (e.g. 3.6 second), as thesample needle 160 moves from inside the seal pack towards the samplesource and into the sample source to aspirate the sample. In the“double” sequence, the predetermined amount of time of washing thesample needle 160 may be between 14-16 seconds (e.g. 15 second), as thesample moves towards the sample source and into the sample source toaspirate the sample. The time for the washing cycle in the “double”sequence is approximately double or slightly more than double the timein the “normal” sequence.

In the “double” sequence, a movement speed of the sample needle 160 frominside the seal pack 100 to the sample source may be reduced, slowed,throttled, etc. to extend the predetermined amount of wash time from 3-6seconds to 14-16, without pausing the movement of the needle 160, ascompared to a movement speed of the sample needle in the “normal”sequence. In previous, known wash sequences, a movement of the needle160 would be paused for a predetermined amount of time (e.g. 14 seconds)while the sample needle 160 was in the position shown in FIG. 3, whereinthe wash fluid was only contacting and moving around the wash frit 35.Thus, by not pausing and continuously but controllably reducing amovement speed of the sample needle 160 as the sample needle 160 entersthe sample source, a duration of direct exposure of the exterior surfaceof the sample needle 160 to a wash fluid 5 is thereby increased, whichcan reduce a carryover percentage.

In the “extended” sequence, the predetermined amount of wash time as thesample needle 160 moves towards the sample source to aspirate the samplemay be equivalent to the “double” sequence, but may also include anadditional washing step for a predetermined amount of time as the sampleneedle 160 moves away from the sample source and returns to an originalposition within the seal pack 100. The predetermined amount of time ofthe additional washing step (e.g. 14-16 seconds) may be equivalent tothe predetermined amount of time for the “double” sequence. In previous,known wash sequences, a movement of the needle 160 would be paused for apredetermined amount of time (e.g. 40 seconds) while the sample needle160 was in the position shown in FIG. 3, wherein the wash fluid was onlycontacting and moving around the wash fit 35. Thus, by not pausing andcontinuously but controllably reducing a movement speed of the sampleneedle 160 as the sample needle 160 enters the sample source and returnsto the interior of the seal pack 100, a duration of direct exposure ofthe exterior surface of the sample needle 160 to a wash fluid 5 isthereby further increased, which can reduce a carryover percentage.

During the wash sequence described herein, the continuous washing of theexterior surface of the sample needle 160 may occur axially along thesample needle 160 in a vertical direction, within a central pathway 165of the seal pack 100. For instance, a wash fluid 5 may directly contactthe exterior surface of the sample needle 160 during the continuouswashing. Furthermore, the sample needle 160 may only move up and downwithin the seal pack 100 during the continuous washing of the washsequence, and the sample needle 160 may not be relocated to a separatecomponent for washing, remaining within the central pathway 165 of theseal pack 100. Using this wash sequence with the seal pack 100 mayachieve a carryover percentage is equal to or less than 0.0025%.

FIG. 9 depicts a graphical illustration of achieving a carryoverpercentage below 0.0025% using the seal pack of FIG. 5 and the “normal”wash sequence, in accordance with the embodiments of the presentinvention. The carryover percentage well below 0.0025% may be achievedusing the seal pack 100 with the other wash sequences described above.Carryover percentage may refer to the presence of an analyte after ablank having no sample is injected into the analytic flow path. SystemsQualification Tests (SQT) may be performed to test a carryoverpercentage. To test for a carryover percentage, a blank having no sampleand only mobile phase (e.g. solvent) is first injected into the analyticflow path to show that the sample needle 160 is clean. Then, a carryoverstandard 201 of sample is injected into the analytic flow path. In FIG.9, the carryover standard injection was 0.0025%. Next, a challengesample containing a sample is injected into the analytic flow path.After the challenge sample is injected, one or more blanks 202 (e.g. nosample, only mobile phase) may again be injected into the analytic flowpath. FIG. 9 indicates the peak carryover percentage for the carryoverstandard injection at 201 p, and indicates the peak carryover percentagefor two blanks after the challenge sample was injected at 202 p. As canbe seen graphically in FIG. 9, the peak carryover percentage after thechallenge sample was injected was well below 0.0025% (i.e. 0%). Thesample used in the SQT shown in FIG. 9 is caffeine. However, the sealpack 100 using the “normal” wash sequence achieves a carryoverpercentage below 0.0025% and at 0 (i.e. carryover) for other samples,such as anthracene, diphenhydramine, oxybutynin, and sulfadimethoxine.Accordingly, the seal pack 100 may reduce or eliminate a carryoverpercentage as compared to previous, known seal packs.

While this disclosure has been described in conjunction with thespecific embodiments outlined above, it is evident that manyalternatives, modifications and variations will be apparent to thoseskilled in the art. Accordingly, the preferred embodiments of thepresent disclosure as set forth above are intended to be illustrative,not limiting. Various changes may be made without departing from thespirit and scope of the invention, as required by the following claims.The claims provide the scope of the coverage of the invention and shouldnot be limited to the specific examples provided herein.

What is claimed is:
 1. A seal pack of a sample manager of a liquidchromatography system, the seal pack having an upper body portion, amiddle body portion, and a lower body portion, which forms a generalbody structure of the seal pack, the seal pack comprising: a centralflow path extending vertically through the seal pack, the central flowpath accommodating a sample needle; a wash inlet disposed in the upperbody portion, configured to receive a wash solution, the wash inletconnecting to the central flow path by a wash inlet flow path; a firstwash path disposed in the upper body portion and connected to thecentral flow path, the first wash path being vertically offset from thewash inlet; a connecting wash path extending through the upper bodyportion, the middle body portion, and the lower body portion, theconnecting wash path connecting the first wash path to a second washpath disposed in the lower body portion, wherein the second wash path isconnected to the central flow path; a third wash path disposed in thelower body portion, the third wash path being vertically offset from thesecond wash path; and a wash outlet disposed in the middle body portionconnected to the third wash path by an intermediate flow path, the washoutlet includes a wash outlet flow path and is fluidically connected toa suction pump for drawing the wash solution through the seal pack. 2.The seal pack of claim 1, wherein, when the wash solution flows from thewash inlet to the first wash path, the wash solution flows axially alongthe sample needle in a vertical direction to directly wash the sampleneedle, further wherein, when the wash solution flows from the secondwash path to the third wash path, the wash solution flows axially alongthe sample needle in a vertical direction to directly wash the sampleneedle.
 3. The seal pack of claim 1, wherein the seal pack does notinclude a lower wash frit.
 4. The seal pack of claim 1, furthercomprising an upper wash frit retainer and an upper wash frit, whereinthe sample needle passes through the upper wash frit.
 5. The seal packof claim 1, further comprising a bushing disposed within the lower bodyportion, the bushing having a central bore for receiving the sampleneedle as the sample needle moves toward a sample source, wherein thebushing is comprised of a non-metal material and prevents damage to thesample needle from contacting a metal surface of the seal pack as thesample needle moves towards and away from the sample source.
 6. The sealpack of claim 1, wherein the wash solution is flowing through the sealpack as the sample needle is moving within the seal pack.
 7. The sealpack of claim 1, further comprising a first high-pressure seal and asecond high-pressure seal, the first high-pressure seal and the secondhigh-pressure seal are disposed within the middle body portion, and forma seal around the sample needle at a point where a sample is injectedinto an analytic flow path.
 8. The seal pack of claim 1, wherein acarryover percentage is equal to or less than 0.0025%.